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Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo

Oncogene volume 25, pages 1753–1762 (2006)Cite this article

Abstract

Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is critical for the initiation of mitosis. Accumulating data indicate that the deregulation of cyclin B1 is tightly linked to neoplastic transformation. To study the phenotype and the potential preclinical relevance, we generated HeLa cell lines stably transfected with the plasmids encompassing short hairpin RNA (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells. In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

Cdks:

Cyclin-dependent kinases

GFP:

Green fluorescent protein

siRNA:

Small interfering RNA

shRNA:

Short hairpin RNA

XIAP:

X-chromosome linked inhibitor of apoptosis

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Acknowledgements

We thank Dr B Martin for his critical reading and Kai Kleiber for layout work. This work is supported by the Nationales Genomforschungsnetz (01GS0104), the Deutsche Krebshilfe (10-1212-St 1), the Deutsche Forschungsgemeinschaft (STR/8-1).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, School of Medicine, JW Goethe-University, Frankfurt, Germany

    J Yuan, A Krämer, Y Matthess, B Spänkuch, R Gätje, M Kaufmann & K Strebhardt

  2. Department of Medical Microbiology, Immunology and Cell Biology & Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, USA

    R Yan

  3. Department of Otorhinolaryngology, School of Medicine, JW Goethe-University, Frankfurt, Germany

    R Knecht

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  1. J Yuan
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Correspondence to J Yuan.

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Yuan, J., Krämer, A., Matthess, Y. et al. Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo. Oncogene 25, 1753–1762 (2006). https://doi.org/10.1038/sj.onc.1209202

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